Purpose. The study aimed to assess impact of CYP2C19, CYP2C9, CYP2D6, and UGT1A1 gene-associated pharmacotherapy on the patterns of adverse drug reactions (ADRs) in the random-SMS-initiated online survey population sample. Methods. Random adult customers of T2 Telecommunication Company were invited using Target-SMS software. Online questionnaire included questions on clinical-pharmacology, demographic, and other health-related characteristics. Pharmacogenetic (PGx) genes associated with individual cases of pharmacotherapy were identified using PharmGKB resources. Sum of CYP2C19, CYP2C9, CYP2D6, and UGT1A1 genes involved in given pharmacotherapy case was referred to as PGx drug index (PGxDi). A total of 2149 respondents were enrolled; 83 participants were assigned to the pilot group to receive PGx testing for actionable CYP2C19, CYP2C9, CYP2D6, and UGT1A1 genetic variants. Results. Pharmacotherapy was reported by 1456 respondents (67.8%); 265 participants (18.2%) reported major polypharmacy. PGxDi values correlated with the presence of cardiovascular diseases, diabetes mellitus, endocrine, musculoskeletal ( p < 0.0001), and urological diseases ( p < 0.01). PGxDi values were significantly associated with history of iatrogenic tinnitus and/or hearing loss ( p < 0.0001), muscle/joint pain/tendon rupture; eye conditions; and dyssomnias ( p < 0.01). Self-medication-seeking behavior negatively correlated with PGxDi ( p < 0.01). Proneness to ADRs correlated with the numbers of loss of function CYP2C19, CYP2C9, CYP2D6, and UGT1A1 variants in the pilot group ( r = 0.2291, p = 0.04361). Conclusions. The involvement of CYP2C19, CYP2C9, CYP2D6, and UGT1A1 genes in pharmacotherapy may significantly affect drug safety. Complications of PGx pharmacotherapy may be reduced by taking medication history, performing dose titration, and practicing medical minimalism.